This project is based on the concept that prostate cancers can be classified based on the molecular pathways deregulated by mutations in oncogenes or tumor suppressor genes. Drugs targeted against a specific molecular pathway should be most effective in those tumors which show a defect in that pathway. We will test this hypothesis in prostate cancer patients whose tumors have deletions of the PTEN tumor suppressor gene. Loss of PTEN leads to upregulation of a signal transduction pathway involving the Akt and mTOR kinases. Our preclinical data shows selective growth inhibition of PTEN null prostate cancers with a specific inhibitor of MTOR called CCI-779, which is a derivative of rapamycin. We will conduct clinical trims in prostate cancer patients whose tumors lack PTEN. Because prostate cancer is heterogeneous, these trials require molecular classification of the tumor prior to treatment. We will also monitor the effect of the mTOR inhibitor on the Akt/mTOR signaling pathway in the tumor. Finally, we will perform further preclinical laboratory studies to optimize the use of CCI-779 in hormone-refractory prostate cancer.